BDBM50073389 (-)-rosiglitazone CHEMBL121106 ROSIGLITAZONE
BDBM28761 rosiglitazone
CHEBI:50122 Avandia US10744117, Compound Rosiglitazone Avandamet Rosiglitazone US9562012, rosiglitazone BDBM50030474 Avandaryl BRL-49653
Avandia [3H]rosiglitazone BDBM28681 Brl-49653 5-[(4-{2-[methyl(pyridin-2-yl)amino]ethoxy}phenyl)methyl]-1,3-thiazolidine-2,4-dione ROSIGLITAZONE MALEATE rosiglitazone BRL 49653 cid_5281055 CHEMBL121
(5R)-5-(4-{2-[methyl(pyridin-2-yl)amino]ethoxy}benzyl)-1,3-thiazolidine-2,4-dione ROSIGLITAZONE (+)-rosiglitazone BDBM50073388
BRL-49653C Avandia 5-{4-[2-(Methyl-pyridin-2-yl-amino)-ethoxy]-benzyl}-thiazolidine-2,4-dione; compound with (Z)-but-2-enedioic acid BDBM50129732 5-{4-[2-(Methyl-pyridin-2-yl-amino)-ethoxy]-benzyl}-thiazolidine-2,4-dione; compound with but-2-enedioic acid CHEMBL843 Rosiglitazone ROSIGLITAZONE MALEATE BRL-49653
- Parks, DJ; Tomkinson, NC; Villeneuve, MS; Blanchard, SG; Willson, TM Differential activity of rosiglitazone enantiomers at PPAR gamma. Bioorg Med Chem Lett 8: 3657-8 (1999)
- Toyota, Y; Nomura, S; Makishima, M; Hashimoto, Y; Ishikawa, M Structure-activity relationships of rosiglitazone for peroxisome proliferator-activated receptor gamma transrepression. Bioorg Med Chem Lett 27: 2776-2780 (2017)
- Geldenhuys, WJ; Funk, MO; Awale, PS; Lin, L; Carroll, RT A novel binding assay identifies high affinity ligands to the rosiglitazone binding site of mitoNEET. Bioorg Med Chem Lett 21: 5498-501 (2011)
- Liu, J; Huang, Z; Ma, W; Peng, S; Li, Y; Miranda, KM; Tian, J; Zhang, Y Design and synthesis of rosiglitazone-ferulic acid-nitric oxide donor trihybrids for improving glucose tolerance. Eur J Med Chem 162: 650-665 (2019)
- Potterat, O; Puder, C; Wagner, K; Bolek, W; Vettermann, R; Kauschke, SG Chlorocyclinones A-D, chlorinated angucyclinones from Streptomyces sp. strongly antagonizing rosiglitazone-induced PPAR-gamma activation. J Nat Prod 70: 1934-8 (2007)
- Seto, S; Okada, K; Kiyota, K; Isogai, S; Iwago, M; Shinozaki, T; Kitamura, Y; Kohno, Y; Murakami, K Design, synthesis, and structure-activity relationship studies of novel 2,4,6-trisubstituted-5-pyrimidinecarboxylic acids as peroxisome proliferator-activated receptor gamma (PPARgamma) partial agonists with comparable antidiabetic efficacy to rosiglitazone. J Med Chem 53: 5012-24 (2010)
- ChEMBL_352521 Displacement of [3H]rosiglitazone from PPARgamma by SPA
- ChEMBL_439784 Displacement of [3H]rosiglitazone from PPAR gamma
- ChEMBL_462571 Displacement of [3H]Rosiglitazone from human PPARgamma
- ChEMBL_692840 Inhibition of human CYP2C8 using rosiglitazone as a substrate
- ChEMBL_1927649 Displacement of [3H]rosiglitazone from PPARgamma (unknown origin)
- ChEMBL_575837 Displacement of [3H]rosiglitazone from human PPARgamma receptor
- ChEMBL_325379 Displacement of [3H]rosiglitazone from human PPAR gamma by SPA assay
- ChEMBL_333345 Displacement of [3H]rosiglitazone from human PPAR gamma by SPA assay
- ChEMBL_460036 Displacement of [3H]rosiglitazone from human PPARgamma receptor by scintillation proximity assay
- ChEMBL_496449 Displacement of [3H]rosiglitazone from mouse PPARgamma receptor by scintillation proximation assay
- ChEMBL_609914 Displacement of [3H]rosiglitazone from rat liver mitochondrial mitoNEET by scintillation counting
- ChEMBL_1559784 Displacement of [3H]rosiglitazone from human recombinant PPARgamma receptor expressed in Escherichia coli
- ChEMBL_321003 Binding affinity for human PPAR gamma construct expressed in bacteria with 3[H] rosiglitazone
- ChEMBL_1813295 Antagonist activity at human PPARgamma expressed in 293H cells assessed as reduction in rosiglitazone-induced transcriptional response preincubated for 30 mins followed by rosiglitazone addition and measured after 16 hrs by reporter gene-based FRET assay
- ChEMBL_1665979 Displacement of [3H]rosiglitazone from human PPARgamma LBD expressed in HEK293 cells by filtration assay
- ChEMBL_460035 Antagonist activity at human PPARgamma receptor assessed as rosiglitazone-induced receptor activation by alphascreen assay
- ChEMBL_946081 Displacement of [3H]-rosiglitazone from GST-tagged PPARgammaLBD (unknown origin) after 1 hr by scintillation proximity assay
- ChEMBL_1487048 Competitive inhibition of CYP2C8 in human liver microsomes assessed as rosiglitazone demethylation after 20 mins by LC-MS/MS analysis
- ChEMBL_1487049 Linear mixed inhibition of CYP2C8 in human liver microsomes assessed as rosiglitazone demethylation after 20 mins by LC-MS/MS analysis
- ChEMBL_460037 Antagonist activity at human PPARgamma receptor in CHO-K1 cells assessed as rosiglitazone-induced receptor activation by cell based reporter assay
- ChEMBL_1481820 Inhibition of CYP2C8 in human liver microsomes using rosiglitazone as substrate preincubated for 20 mins with substrate prior to initiation of reaction with NADPH by HPLC analysis
- ChEMBL_1838769 Displacement of [3H]rosiglitazone from human recombinant PPARgamma LBD expressed in insect cells measured after 24 hrs by scintillation counting analysis
- ChEMBL_766432 Displacement of [3H]-rosiglitazone from human recombinant C-terminal His-tagged cytosolic domain of mitoNEET (32-108) by scintillation proximity assay
- ChEMBL_1633591 Displacement of [3H]rosiglitazone from human recombinant PPAR-gamma receptor expressed in Escherichia coli measured after 120 mins by scintillation counting method
- ChEMBL_636347 Displacement of [3H]rosiglitazone from human PPARgamma ligand binding domain expressed in Escherichia coli BL21 after 12 hrs by liquid scintillation counting
- ChEMBL_1502033 Inhibition of CYP2C8 in human liver microsomes using rosiglitazone as susbtrate incubated for 30 mins prior to substrate addition for 10 mins by LC-MS/MS analysis
- ChEMBL_642067 Antagonist activity at rat PPARgamma-LBD expressed in CHO-K1 cells co-transfected with GAL4 assessed as inhibition of rosiglitazone-induced luciferase activity by transactivation assay
- ChEMBL_642068 Antagonist activity at human PPARgamma-LBD expressed in CHO-K1 cells co-transfected with GAL4 assessed as inhibition of rosiglitazone-induced luciferase activity by transactivation assay
- ChEMBL_642078 Antagonist activity at mouse PPARgamma-LBD expressed in CHO-K1 cells co-transfected with GAL4 assessed as inhibition of rosiglitazone-induced luciferase activity by transactivation assay
- ChEMBL_1493636 Metabolism-dependent inhibition of CYP2C8 in human liver microsomes using rosiglitazone as substrate preincubated for 20 mins with NADPH prior to initiation of reaction with probe substrate by HPLC analysis
- ChEMBL_1840162 Agonist activity at human PPARgamma expressed in African green monkey COS7 cells assessed as increase in receptor transcriptional activity by luciferase reporter gene assay relative to rosiglitazone
- ChEMBL_2170278 Partial agonist activity at recombinant sGSF-PPARgamma (unknown origin) assessed as reduction in rosiglitazone induced CBP-1 recruitment incubated for 1 hr by HTRF competitive assay
- ChEMBL_880133 Displacement of [3H]rosiglitazone from N-terminal His-tagged human PPARgamma ligand binding domain expressed in Escherichia coli BL21 DE3 cells by scintillation proximity assay
- ChEMBL_1620947 Displacement of [3H]rosiglitazone from recombinant human C-terminal His-tagged MitoNEET cytosolic domain (32 to 108 residues) expressed in Escherichia coli BL21 by scintillation proximity assay
- ChEMBL_1620948 Displacement of [3H]rosiglitazone from recombinant human C-terminal His-tagged MitoNEET cytosolic domain (32 to 108 residues) expressed in Escherichia coli BL21 by Cheng-Prusoff analysis
- ChEMBL_1908620 Inhibition of rosiglitazone-activated human TRPC5 channel expressed in HEK293 cells assessed as reduction in Ca2+ current measured at +80 mV with holding potential of -60 mV by Q-patch clamp assay
- ChEMBL_1908668 Inhibition of rosiglitazone-activated rat TRPC5 channel expressed in HEK293 cells assessed as reduction in Ca2+ current measured at +80 mV with holding potential of -60 mV by Q-patch clamp assay
- ChEMBL_1779840 Synergistic agonist activity at human PPARgamma LBD assessed as biotin-labeled PGC1alpha (130 to 154 residues) co-activator recruitment after 1 hr in presence of 0.37 uM rosiglitazone by TR-FRET assay
- ChEMBL_1779841 Synergistic agonist activity at human PPARgamma LBD assessed as biotin-labeled PGC1alpha (130 to 154 residues) co-activator recruitment after 1 hr in presence of 1 uM rosiglitazone by TR-FRET assay
- ChEMBL_1779842 Synergistic agonist activity at human PPARgamma LBD assessed as biotin-labeled PGC1alpha (130 to 154 residues) co-activator recruitment after 1 hr in presence of 10 uM rosiglitazone by TR-FRET assay
- ChEMBL_1867731 Antagonist actvity in pFA-GAL4-DBD fused PPARgamma LBD (unknown origin) transfected in HEK293T cells assessed as inhibition of rosiglitazone-induced PPARgamma transactivation incubated for 24 hrs by luciferase reporter gene assay
- ChEMBL_1867743 Antagonist actvity in sGFP-tagged PPARgamma LBD (unknown origin) assessed as inhibition of rosiglitazone-induced PPARgamma activation incubated for 1 hr in presence of CBP-1 cofactor peptide by HTRF based cofactor recruitment assay
- ChEMBL_544086 Antagonist activity at human PPARgamma receptor expressed in Saccharomyces cerevisiae AH109 co-transfected with mouse CBP assessed as inhibition of rosiglitazone-induced LBD-CBP interaction by alpha-galactosidase based yeast two hybrid assay
- ChEMBL_1750171 Antagonist activity at CMV-fused PPARgamma-LBD-GAL4-DBD (unknown origin) expressed in HEK293T cells assessed as inhibition of rosiglitazone-induced receptor transactivation after 16 hrs by bright-Glo luciferase reporter gene assay
- ChEMBL_1878653 Inverse agonist activity at His6-tagged PPARgamma LBD (unknown origin) assessed as inhibition of rosiglitazone-induced N-terminal biotinylated co-activator SRC1 box2 peptide recruitment measured after 30 mins by TR-FRET assay
- ChEMBL_1898203 Antagonist activity at human PPARgamma LBD expressed in yeast AH109 cells assessed as reduction in rosiglitazone-stimulated PPARgamma/CBP interaction by measuring alpha galactosidase activity using PNP-alpha-Gal as substrate by alpha-galactosidase based yeast-two hybrid assay
- Pharmacological In Vitro Assay Binding assays were performed in 96-well plate format, using a classical filtration assay with a human full length PPARγ construct (GST-PPAR LBD (25 μg/mL)) expressed in bacteria with some modifications regarding the conditionsof the experiments. The membrane-associated PPARγ was used as the biological source as previously described. Binding buffer consisted of 10 mM Tris/HCl, pH 8.2, containing 50 mM KCl and 1 mM dithiothreitol. Membrane preparations (5 μg/mL) were incubated for 180 min at 4°C in the presence of [3H]rosiglitazone (BRL49653, Amersham) (4 nM) and the tested compounds. Nonspecific binding was defined using an excess of unlabeled rosiglitazone (10 μM). Incubation was terminated by the addition of ice-cold 50 mM Tris/HCl buffer pH 7.4, followed by rapid filtrationunder reduced pressure through Whatman GF/C filter plates presoaked with ice-cold buffer, followed by three successive washes with the same buffer. Radioactivity was measured in a TopCount apparatus (Packard).
- PPAR gamma Fluorescence Polarization Assay (IC50) and Cell-Based Transcription Assay (EC50) For PPARgamma, the percentage inhibition was calculated relative to rosiglitazone, which was used as the active site-specific competitive binder. Fluorescence polarization measurements were performed on an LJL Analyst (Molecular Devices, Sunnyvale, CA) using an excitation wavelength of 485 nm and an emission wavelength of 530 nm. IC50, Hill slope, and maximal and minimal inhibition values were calculated in XLfit (IDBS, Guildford, Surrey, UK). EC50 is the concentration of test compounds needed to induce 50% of the maximum luciferase activity in HEK cells transfected with PPAR and Gal4-luciferase reporter construct.
- Competition Binding Assay (Ki) The scintillation proximity assay was performed in 96-well plates containing polylysine-coated yttrium silicate beads, His-PPARgamma-LBD, and [3H]rosiglitazone. Test compounds were tested in 10-point concentration-response curves starting at the indicated concentration. All components were added simultaneously and incubated with gentle shaking for 1 h at room temperature. Scintillation counts were determined in a Microbeta 1450 Wallac Trilux counter (PerkinElmer Life Sciences), reading each well for 1 min. Wells devoid of competitor represented 100% binding. Nonspecific binding was measured by leaving PPARgamma protein out of the scintillation proximity assay reaction. Experiments were repeated three times. Ki values of the ligands were calculated using Graph-Pad Prism version 4.0c for Macintosh (GraphPad Software).
- PPARgamma Agonist Activity Agonist activity of the enantiomers of 5-({p-[2-(5-ethyl-2-pyridyl)ethoxy]phenyl} methyl)-(5-2H)-1,3-thiazolidine-2,4-dione at the peroxisome proliferator-activated receptor gamma (PPARγ) was evaluated in the thyroid receptor-associated protein complex, 220 kDa component (TRAP220) PPARγ coactivator recruitment assay performed at Cerep (France). Briefly, a mixture of labeled PPARγ and tagged TRAP220 coactivator was pre-incubated at room temperature for 30 minutes in the presence of a PPARγ-targeted fluorescence acceptor and test compound. A TRAP220-targeted fluorescence donor was then added and the mixture was incubated for 120 minutes at room temperature. Next, the fluorescence signal was measured and results expressed as a percent of control (10 μM rosiglitazone). A dose response curve was generated for each enantiomer and the experimental data was analyzed using the log(agonist) vs. response (three parameters) non-linear model in GraphPad Prism 6.0 (GraphPad Software, Inc., La Jolla, Calif.), with a fixed Hillslope of 1.
- PPARgamma Agonist Activity Agonist activity of the enantiomers of 5-({p-[2-(5-ethyl-2-pyridyl)ethoxy]phenyl}methyl)-(5-2H)-1,3-thiazolidine-2,4-dione at the peroxisome proliferator-activated receptor gamma (PPARγ) was evaluated in the thyroid receptor-associated protein complex, 220 kDa component (TRAP220) PPARγ coactivator recruitment assay performed at Cerep (France). Briefly, a mixture of labeled PPARγ and tagged TRAP220 coactivator was pre-incubated at room temperature for 30 minutes in the presence of a PPARγ-targeted fluorescence acceptor and test compound. A TRAP220-targeted fluorescence donor was then added and the mixture was incubated for 120 minutes at room temperature. Next, the fluorescence signal was measured and results expressed as a percent of control (10 μM rosiglitazone). A dose response curve was generated for each enantiomer and the experimental data was analyzed using the log(agonist) vs. response (three parameters) non-linear model in GraphPad Prism 6.0 (GraphPad Software, Inc., La Jolla, Calif.), with a fixed Hillslope of 1.
- Activation Assay As an expression vector, a chimera in which DNA binding domain of Gal4, which is a yeast transcription factor, and ligand binding domain of human PPARγ2 are fused, i.e., a fused product between the amino acids 1 to 147 of Gal4 transcription factor and the amino acids 182 to 505 of human PPARγ2, was used. Furthermore, as a reporter vector, a firefly luciferase containing five copies of Gal4 recognition sequence in the promoter region was used. Plasmid transfection to the cells was performed according to a method which uses jetPEI (trade name, manufactured by Funakoshi Co., Ltd., Tokyo, Japan). Furthermore, β-galactosidase expression vector was employed as an internal standard. After the transfection into the cells, the medium was replaced with a DMEM medium (containing 1% serum) added with the test compound, and the cells were further cultured for 16 hours. After that, the luciferase activity and β-galactosidase activity in the cell lysis solution were measured. Meanwhile, for the present test, dimethylsulfoxide (DMSO) was used for dissolution and dilution of the test compounds, and during the cell treatment, the DMSO concentration in DMEM medium (containing 1% serum) was adjusted to 0.1%. As a positive compound, rosiglitazone (trade name, manufactured by ALEXIS Corporation, Switzerland) was used.